Significance The significance of this project is twofold. First, transgenic cells expressing Nerve Growth Factor (NGF) will help us understand mechanisms of neuronal plasticity and repair the adult primate brain, and secondly, they could have potential for therapy in the treatment of neurodegenerative disorders such as Alzheimer[unreadable]s Disease. Objectives Gene therapy offers a means of delivering therapeutic substances into the central nervous system in a well-targeted, regionally-restricted, safe, efficient and long-term manner. In these studies, we are examining the effects of grafts of autologous cells genetically modified to produce nerve growth factor (NGF) on the survival and function of degenerating basal forebrain cholinergic neurons in adult and aged primates. Results Findings to date have revealed that primary autologous primate cells genetically modified to produce NGF survive for extended periods in the brain and do not elicit adverse effects. In vivo gene expression has been documented for periods of at least 8 months. NGF-secreting cell grafts but not control cell grafts reduce both lesion-induced cholinergic neuronal degeneration and age-related basal forebrain cholinergic neuronal atrophy. Future Directions These findings suggest that NGF gene therapy may be a useful means of reducing cholinergic neuronal degeneration in neurodegenerative disorders such as Alzheimer[unreadable]s disease. Continued studies are underway that are directed toward beginning human clinical trials of NGF gene therapy for Alzheimer[unreadable]s disease.